BIOORGANIC CHEMISTRY
·
2017
·
IF 3.231
Ren-Chao Zheng,Jian-Qiang Jin,Zhe-Ming Wu,Xiao-Ling Tang,Li-Qun Jin,Yu-Guo Zheng
2-Chloronicotinic acid (2-CA) is an important building block for a series of agrochemicals and pharmaceuticals. Amidase-catalyzed hydrolysis of 2-chloronicotinamide is one of the most attractive approaches for 2-CA production. However, development of the bioprocess was plagued by low activity of amidase for 2-chloronicotinamide. In this work, an amidase signature (AS) family amidase from Pantoea sp. ( Pa -Ami), with superior activity for nicotinamide and its chlorinated derivatives, was exploited and characterized. Kinetic analysis and molecular docking clearly indicated that chlorine substitution in the pyridine ring of nicotinamide, especially the substitution at 2-position led to a dramatic decrease of Pa -Ami activity. The productivity of the bioprocess was significantly improved using fed-batch mode at low reaction temperature and 2-CA was produced as high as 370 mM with a substrate conversion of 94.2%. These results imply that Pa -Ami is potentially promising biocatalyst for industrial production of 2-CA.
研究领域:
生物化学
·
工业酶学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Catalysis
·
2023
·
IF 12.9
Zhe-Ming Wu,Feng Xie,Wen Zheng,Chang-Feng Liu,Chao-Ping Lin,Ren-Chao Zheng,Yu-Guo Zheng
Amidases are robust biocatalysts for the industrial synthesis of carboxylic acids. Amidase-catalyzed hydrolysis of 2-chloronicotinamide is regarded as a promising route for 2-chloronicotinic acid production, which is an important building block for agrochemicals and pharmaceuticals. However, the o-substituted Cl of the pyridine ring caused a strong electronic effect and steric hindrance. Engineering access tunnels is one of the most efficient strategies to improve catalytic efficiency by adjusting the transfer efficiency of ligands. Herein, we engineered a twisted access tunnel of amidase and the mutant PaAmiM1A378V+V402L+L403V was achieved, which exhibited increased catalytic efficiency toward 2-chloronicotinamide. Tunnel analysis, molecular dynamics simulations, and quantum mechanical calculations revealed that the straightened tunnel significantly improved the transport efficiency and simultaneously facilitated substrate binding and nucleophilic attack. With the best mutant as a biocatalyst, 1330 mM product was accumulated within 2 h and a high space-time-yield of 2515 gproduct L–1 d–1 was achieved, which is the highest ever reported. These results lay the foundation for industrial production of 2-chloronicotinic acid and give important guidance for engineering amidases into versatile biocatalysts.
研究领域:
生物催化
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化学工程
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酶工程
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有机化学
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药学
✓ 已验证
产品关联
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2020
·
IF 4.089
H. Liu,X. Yang,S. Cao,F. Yu,S. Long,J. Chen,M. Zhang,S. Parkin,T. Li,Z. Yang
A series of N-phenyl-2-hydroxynicotinanilides (PHNAs) have been synthesized, and their crystal structures have been investigated. The identity of these compounds is revealed to be the tautomer of PHNAs, i.e., 2-oxo-1,2-dihydropyridine-3-carboxylic acid phenylamides, compounds with both amide and lactam functionalities. Among these compounds, those with no or negligible steric hindrance take a near planar conformation and form lactam–lactam dimers, not the widely observed amide NH···O═C hydrogen bond chains, while those with steric hindrance take a twisted conformation and form an amide NH···O═C (lactam) hydrogen bond. A succinct theoretic study combining conformational analysis and molecular electrostatic potential surfaces (MEPS) survey provided a reasonable explanation of the formation of these two different hydrogen bond motifs.
研究领域:
化学
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晶体学
·
理论计算
✓ 已验证
产品关联
DOI
高影响因子
CRYSTENGCOMM
·
2022
·Vol. 25
·期 3
·432-443
·
IF 3.756
Yuping Li,Yang Tao,Yunping Zhoujin,Fang Zhao,Peng-Yu Liang,Sean Parkin,Tonglei Li,Pan-Pan Zhou,Sihui Long
Substituent size and isomerization play an important role in the polymorphism of 2-(naphthalen-n-ylamino)-benzoic acids (n = 1, 2; 2-NBAs) as each of the two previously investigated 2-NBAs was found to be polymorphic, while their parent compound fenamic acid (FA) has only one form discovered. 2-(Naphthalen-1-ylamino)-nicotinic acid (1) and 2-(naphthalen-2-ylamino)-nicotinic acid (2) (2-NNA) are isosteric compounds of 2-NBAs, and 2-(2,3-dimethyl-phenylamino)-nicotinic acid (3) and 2-(3,4-dimethyl-phenylamino)-nicotinic acid (4) are 2-NNA analogues with similar substitution patterns. All four compounds are clonixin analogues. The polymorphism of these four compounds was investigated. One solvent-free form (1-A) and one hydrate (1-H) were discovered for 1, three forms (2-I, 2-II, and 2-III) were obtained for 2, and one form was found for 3 and 4. The four systems were characterized by single-crystal XRD (SCXRD) and powder XRD (PXRD), and structural properties were compared among the crystals of the four compounds, their isosteres, and other related analogues. The phase behavior of the four systems was studied with differential scanning calorimetry (DSC). Thermogravimetric analysis (TGA) was used to investigate the dehydration of 1-H. Computational studies such as stable conformer search, π–π interaction energy calculation, and non-covalent interaction (NCI) analysis were performed to shed light on the rise of polymorphism, and the relative contribution of various intermolecular interactions to the overall stability of the crystals. The study confirmed the effect of substituent size, thus the consequent π–π interactions, on the hydrate formation of compound 1 and polymorphism of compound 2.
研究领域:
物理化学
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晶体学
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材料科学
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药物化学
✓ 已验证
产品关联
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2023
·
IF 3.8
Yunping Zhoujin,Yuping Li,Peng-Yu Liang,Pan-Pan Zhou,Sean Parkin,Tonglei Li,Faquan Yu,Sihui Long
A series of phenylalkylamino-nicotinic acids (1–4) were synthesized by varying the length of the linker between the pyridine and benzene rings, and their polymorphism was investigated. Under the same crystallization conditions, one crystal form was found for compounds 1 and 2, three forms were obtained for compound 3, and two forms were harvested for compound 4. A detailed conformational analysis was performed, and the polymorphism of 3 and 4 was found to be caused by the anti and/or gauche conformation of specific sigma bonds within them. However, there appears to be no correlation between the number of polymorphs and sigma bonds, and the rotation of which sigma bond(s) is responsible for the polymorphism could not be predicted. Phase behavior studies by differential scanning calorimetry (DSC) revealed a phase transition from 4-I with a small asymmetric unit (Z′ = 1) to 4-II with a larger asymmetric unit (Z′ = 2). Computational studies including Hirshfeld surface analysis and independent gradient model (IGM) analyses were performed to highlight the most significant intermolecular interactions in the crystals.
研究领域:
化学
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材料科学
·
晶体学
✓ 已验证
产品关联
DOI
高影响因子
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